Abstract Sepsis is a major public health concern and the primary cause of death in the intensive care unit, accounting for more than $20 billion (5.2%) of total US hospital costs in 2011. Sepsis can lead to a life-threatening drop in blood pressure termed septic shock, which can quickly lead to the failure of vital organs such as lungs, kidneys, and liver, and eventually to death. Nearly all sepsis cases are associated with bacterial or fungal blood stream infection (BSI). Due to the rapid progression of sepsis, the therapeutic window is very short. In order for hospitals to qualify for Medicare in the US, physicians are required to treat suspected BSI within 3 hours of an empirical BSI diagnosis. The current standard of care until definite diagnosis of pathogen is reached by immediate intervention with broad-spectrum empirical antimicrobial therapy and supportive treatment, have been shown to have the greatest impact on outcomes. However, the broad spectrum drugs are not always well tolerated, often do not target fungal infections and are expensive. Therefore a major hurdle of treating sepsis caused by BSI remains reaching a fast diagnosis of the causative pathogen. A variety of nucleic acid based molecular tests can be performed on positive cultures for identifying the pathogen(s) and characterizing their antibiotic susceptibility. However, the average time to receive a positive culture result is slow (2-6 days), and species identification and drug sensitivity profiling prolongs the process even further. We offer the use of the TangenDx Molecular Diagnostic Platform for BSI Detection. Tangen?s unique technological advantage is in capturing and concentrating the pathogens from a raw sample before they go into the instrument. Tangen is able to achieve high sensitivity of detection directly from whole blood because of development of unique laser-drilled kapton filters that enable large blood volumes, ranging from tens of milliliters to tens of microliters, to be concentrated by the LVCTM technology. For BSI, the TangenDx will provide a diagnostic sensitivity that is equal to or superior to blood culture methods and deliver a diagnosis and pathogen ID in less than 2 hours total. A major hurdle to using nucleic acid based molecular assays to directly detect blood stream pathogens is the fact that the concentration of cells per ml of blood is very low (1 CFU/ml of blood). Our approach to overcome this problem involves two strategies; first targeting multi-copy gene regions (e.g. Mitochondrial, transposons or rRNA genes), and second performing a global Whole Genome Amplification step in the central chamber of the Assay disk prior to distributing the amplified genomic material to the 33/35 Assay wells. We have demonstrated that it is feasible to detect as few as 10 genome copies with LAMP primers targeting rRNA multi-copy genes and that WGA can be successfully applied to the captured genomes prior to the LAMP reactions. We will also test the fully integrated system with spiked blood samples. Such a rapid diagnostics with faster turnaround time could enable rapid selection of appropriate treatment and reduce the 15% to 40% mortality sepsis rate.